The objective of this Phase II proposal is to optimize a procedure for producing a large number of genetically identical rabbits by serial nuclear transplantation. The use of genetically identical rabbits would decrease the number of animals needed for experimentation. Development of a highly efficient nuclear cloning strategy will make it commercially feasible to develop and produce rabbit models for specific human disorders. Over the coming decade, these animals could capture a share of the potentially lucrative market in genetically engineered animal disease models. The optimized protocol will be applied to Watanabe heritable hyperlipidemic (WHHL) rabbits, the only genetic animal model for familial hypercholesterolemia. Reproductive problems currently limited the availability of WHHL rabbits for basic and therapeutic research.